Comparative study of Mg/Al- and Zn/Al-layered double hydroxide-perindopril erbumine nanocomposites for inhibition of angiotensin-converting enzyme

Int J Nanomedicine. 2012:7:4251-62. doi: 10.2147/IJN.S32267. Epub 2012 Aug 3.

Abstract

The intercalation of a drug active, perindopril, into Mg/Al-layered double hydroxide for the formation of a new nanocomposite, PMAE, was accomplished using a simple ion exchange technique. A relatively high loading percentage of perindopril of about 36.5% (w/w) indicates that intercalation of the active took place in the Mg/Al inorganic interlayer. Intercalation was further supported by Fourier transform infrared spectroscopy, and thermal analysis shows markedly enhanced thermal stability of the active. The release of perindopril from the nanocomposite occurred in a controlled manner governed by pseudo-second order kinetics. MTT assay showed no cytotoxicity effects from either Mg/Al-layered double hydroxide or its nanocomposite, PMAE. Mg/Al-layered double hydroxide showed angiotensin-converting enzyme inhibitory activity, with 5.6% inhibition after 90 minutes of incubation. On incubation of angiotensin-converting enzyme with 0.5 μg/mL of the PMAE nanocomposite, inhibition of the enzyme increased from 56.6% to 70.6% at 30 and 90 minutes, respectively. These results are comparable with data reported in the literature for Zn/Al-perindopril.

Keywords: Chang cells line; aluminum; angiotensin-converting enzyme; ion exchange; layered double hydroxide; magnesium; perindopril erbumine.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adsorption
  • Aluminum Hydroxide / chemistry
  • Aluminum Hydroxide / pharmacokinetics
  • Aluminum Hydroxide / pharmacology*
  • Angiotensin-Converting Enzyme Inhibitors / chemistry
  • Angiotensin-Converting Enzyme Inhibitors / pharmacokinetics
  • Angiotensin-Converting Enzyme Inhibitors / pharmacology*
  • Cell Line
  • Cell Survival / drug effects
  • Delayed-Action Preparations
  • Drug Combinations
  • Hippurates / analysis
  • Hippurates / metabolism
  • Humans
  • Hydrogen-Ion Concentration
  • Magnesium Hydroxide / chemistry
  • Magnesium Hydroxide / pharmacokinetics
  • Magnesium Hydroxide / pharmacology*
  • Nanocomposites / chemistry*
  • Oligopeptides / analysis
  • Oligopeptides / metabolism
  • Peptidyl-Dipeptidase A / chemistry
  • Peptidyl-Dipeptidase A / metabolism
  • Perindopril / chemistry
  • Perindopril / pharmacokinetics
  • Perindopril / pharmacology*
  • Spectrophotometry, Infrared
  • X-Ray Diffraction
  • Zinc / chemistry
  • Zinc / pharmacokinetics
  • Zinc / pharmacology

Substances

  • Angiotensin-Converting Enzyme Inhibitors
  • Delayed-Action Preparations
  • Drug Combinations
  • Hippurates
  • Oligopeptides
  • hippuryl-histidyl-leucine
  • aluminum hydroxide, magnesium hydroxide, drug combination
  • Aluminum Hydroxide
  • Peptidyl-Dipeptidase A
  • Zinc
  • Magnesium Hydroxide
  • hippuric acid
  • Perindopril